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Labeled Compounds (labeled + compound)
Selected AbstractsSynthesis and evaluation of two uncharged 99mTc-labeled derivatives of thioflavin-T as potential tracer agents for fibrillar brain amyloidJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 6 2009K. Serdons Abstract Thioflavin-T is a fluorescent dye for in vitro detection of fibrillar amyloid ,, a protein found in the brain of patients suffering from Alzheimer's disease. We synthesized and biologically evaluated two uncharged 99mTc-labeled derivatives of thioflavin-T. The precursors for labeling were synthesized by coupling an S,S, -bis-triphenylmethyl- N - tert -butoxycarbonyl bis-amino-bis-thiol tetradentate ligand via a propoxy spacer to 2-(4,-aminophenyl)-1,3-benzothiazole at the 6-position or the 2,-position. Deprotection and labeling with 99mTc were done via a one-pot procedure (15% yield) after which the labeled compound was isolated by high performance liquid chromatography (LC). LC in combination with mass spectrometry (MS) was used for identity confirmation of the labeled compounds. Results of electrophoresis and log,P determination supported the assumption that the radiolabeled compounds could cross the blood,brain barrier by passive diffusion. However, in normal mice both compounds showed a low brain uptake 2,min post injection. They were mainly excreted through the hepatobiliary system, with some accumulation in the stomach. Sixty minutes after intravenous injection, 37% of the 99mTc-activity in the blood corresponded to the original compound. In view of the low brain uptake, it is concluded that the studied 99mTc-labeled derivatives of thioflavin-T are not suitable as tracer agents for in vivo visualization of amyloid in brain. Copyright © 2009 John Wiley & Sons, Ltd. [source] An investigation of the 125I-radioiodination of colchicine for medical purposesJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 1 2009K. M. El-Azony Abstract A procedure for radioiodination of colchicine with iodine-125 is carried out via an electrophilic substitution reaction. The reaction parameters studied were colchicine concentration, pH of the reaction mixture, reaction time, temperature, different oxidizing agents and different organic media to optimize the conditions for the labeling of colchicine and to obtain a high radiochemical yield of the 125I-colchicine (125I-Col). Using 3.7,MBq of Na125I, 1.25,mM of colchicine as substrate, 1.1,mM of chloramine-T (CAT) as oxidizing agent in ethanol at 60°C for 5,min, a maximum radiochemical yield of 125I-Col (60%) was obtained. The specific activity of 125I-Col obtained was 44.4,MBq/0.5,mmol, and the labeled compound was not completely separated and purified from Col by means of high-pressure liquid chromatography (HPLC), so the uncertainty in the purity may affect the distribution and clearance routes due to the expected competition between 125I-Col and Col. The biological distribution in normal mice indicates the suitability of radioiodinated colchicine for imaging of muscles. Copyright © 2008 John Wiley & Sons, Ltd. [source] Synthesis of a 13C labeled N -cyclopropylamine tetrahydropyridine derivativeJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 10 2002Simon Kuttab Abstract The synthesis of 1-(2- 13C)-cyclopropyl-4-phenyl-1,2,3,6-tetrahydropyridine (8) is reported. Attempts were first made to prepare labeled cyclopropylamine via a cyclopropanation/Curtius rearrangement sequence, but the yields were too modest to be suitable for the synthesis of a labeled compound. The preparation of 8 was achieved via cyclopropanation of the N -formyl tetrahydropyridine derivative 21 using the Grignard reagent of ethyl bromide and Ti(O- iPr)4 as a catalyst. The synthesis proceeded in high yield (82%). The method has a wide potential for the synthesis of other cyclopropyl ring labeled and substituted cyclopropyl ring labeled tetrahydropyridine dervatives which can be used in Monoamine Oxidase (MAO) and Cyt P450 enzymes mechanistic studies. Copyright © 2002 John Wiley & Sons, Ltd. [source] Biological hydroperoxides and singlet molecular oxygen generationIUBMB LIFE, Issue 4-5 2007Sayuri Miyamoto Abstract The decomposition of lipid hydroperoxides (LOOH) into peroxyl radicals is a potential source of singlet molecular oxygen (1O2) in biological systems. Recently, we have clearly demonstrated the generation of 1O2 in the reaction of lipid hydroperoxides with biologically important oxidants such as metal ions, peroxynitrite and hypochlorous acid. The approach used to unequivocally demonstrate the generation of 1O2 in these reactions was the use of an isotopic labeled hydroperoxide, the 18O-labeled linoleic acid hydroperoxide, the detection of labeled compounds by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) and the direct spectroscopic detection and characterization of 1O2 light emission. Using this approach we have observed the formation of 18O-labeled 1O2 by chemical trapping of 1O2 with anthracene derivatives and detection of the corresponding labeled endoperoxide by HPLC-MS/MS. The generation of 1O2 was also demonstrated by direct spectral characterization of 1O2 monomol light emission in the near-infrared region (, = 1270 nm). In summary, our studies demonstrated that LOOH can originate 1O2. The experimental evidences indicate that 1O2 is generated at a yield close to 10% by the Russell mechanism, where a linear tetraoxide intermediate is formed in the combination of two peroxyl radicals. In addition to LOOH, other biological hydroperoxides, including hydroperoxides formed in proteins and nucleic acids, may also participate in reactions leading to the generation 1O2. This hypothesis is currently being investigated in our laboratory. [source] Synthesis and evaluation of two uncharged 99mTc-labeled derivatives of thioflavin-T as potential tracer agents for fibrillar brain amyloidJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 6 2009K. Serdons Abstract Thioflavin-T is a fluorescent dye for in vitro detection of fibrillar amyloid ,, a protein found in the brain of patients suffering from Alzheimer's disease. We synthesized and biologically evaluated two uncharged 99mTc-labeled derivatives of thioflavin-T. The precursors for labeling were synthesized by coupling an S,S, -bis-triphenylmethyl- N - tert -butoxycarbonyl bis-amino-bis-thiol tetradentate ligand via a propoxy spacer to 2-(4,-aminophenyl)-1,3-benzothiazole at the 6-position or the 2,-position. Deprotection and labeling with 99mTc were done via a one-pot procedure (15% yield) after which the labeled compound was isolated by high performance liquid chromatography (LC). LC in combination with mass spectrometry (MS) was used for identity confirmation of the labeled compounds. Results of electrophoresis and log,P determination supported the assumption that the radiolabeled compounds could cross the blood,brain barrier by passive diffusion. However, in normal mice both compounds showed a low brain uptake 2,min post injection. They were mainly excreted through the hepatobiliary system, with some accumulation in the stomach. Sixty minutes after intravenous injection, 37% of the 99mTc-activity in the blood corresponded to the original compound. In view of the low brain uptake, it is concluded that the studied 99mTc-labeled derivatives of thioflavin-T are not suitable as tracer agents for in vivo visualization of amyloid in brain. Copyright © 2009 John Wiley & Sons, Ltd. [source] Synthesis of 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoinJOURNAL OF LABELLED COMPOUNDS AND RADIOPHARMACEUTICALS, Issue 14 2003Hongbin Yu Abstract 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoin was synthesized from the oxidation of 1,7,NH2 - 15N3 -8-oxo-7,8-dihydro-2,-deoxyguanosine with 2 equivalents of Ir(IV) in pH 4.5 potassium phosphate buffer. The synthesis of 1,7,NH2 - 15N3 -8-oxo-7,8-dihydro-2,-deoxyguanosine started with bromination of 1,7,NH2 - 15N3 -2,-deoxyguanosine. The resulting 1,7,NH2 - 15N3 -8-bromo-7,8-dihydro-2,-deoxyguanosine reacted with sodium benzyloxide to afford 1,7,NH2 - 15N3 -8-benzyloxy-7,8-dihydro-2,-deoxyguanosine. Subsequent catalytic transfer hydrogenation of 1,7,NH2 - 15N3 -8-benzyloxy-7,8-dihydro-2,-deoxyguanosine with cyclohexene and 10% Pd/C yielded 1,7,NH2 - 15N3 -8-oxo-7,8-dihydro-2,-deoxyguanosine. Purification of 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoin was first carried out on a C18 column and the product was further purified on a graphite column. ESI-MS was used to confirm the identity and to determine the isotopic purity of all the labeled compounds. The isotopic purity of 3,7,8- 15N3 -N1 -(, -D- erythro -pentofuranosyl)-5-guanidinohydantoin was 99.4 atom% based on LC-MS measurements. Copyright © 2003 John Wiley & Sons, Ltd. [source] Functional Characterization of the Recombinant N -Methyltransferase Domain from the Multienzyme Enniatin SynthetaseCHEMBIOCHEM, Issue 9 2007Till Hornbogen Dr. Abstract A 51 kDa fusion protein incorporating the N -methyltransferase domain of the multienzyme enniatin synthetase from Fusarium scirpi was expressed in Saccharomyces cerevisiae. The protein was purified and found to bind S -adenosyl methionine (AdoMet) as demonstrated by cross-linking experiments with 14C-methyl-AdoMet under UV irradiation. Cofactor binding at equilibrium conditions was followed by saturation transfer difference (STD) NMR spectroscopy, and the native conformation of the methyltransferase was assigned. STD NMR spectroscopy yielded significant signals for H2 and H8 of the adenine moiety, H1' of D -ribose, and SCH3 group of AdoMet. Methyl group transfer catalyzed by the enzyme was demonstrated by using aminoacyl- N -acetylcysteamine thioesters (aminoacyl-SNACs) of L -Val, L -Ile, and L -Leu, which mimic the natural substrate amino acids of enniatin synthetase presented by the enzyme bound 4,-phosphopantetheine arm. In these experiments the enzyme was incubated in the presence of the corresponding aminoacyl-SNAC and 14C-methyl-AdoMet for various lengths of time, for up to 30 min. N -[14C-Methyl]-aminoacyl-SNAC products were extracted with EtOAc and separated by TLC. Acid hydrolysis of the isolated labeled compounds yielded the corresponding N -[14C-methyl] amino acids. Further proof for the formation of N - 14C-methyl-aminoacyl-SNACs came from MALDI-TOF mass spectrometry which yielded 23,212 Da for N -methyl-valyl-SNAC, accompanied by the expected postsource decay (PSD) pattern. Interestingly, L -Phe, which is not a substrate amino acid of enniatin synthetase, also proved to be a methyl group acceptor. D -Val was not accepted as a substrate; this indicates selectivity for the L isomer. [source] | ||||||||||